Predictors of Response to Biventricular Pacing in Heart Failure
| Status: | Completed |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 1/7/2018 |
| Start Date: | June 2005 |
| End Date: | June 2012 |
Heart Failure (HF) is a disease of epidemic proportion in the U.S. affecting over 5 million
individuals. It is estimated that in the next year nearly 400,000 new cases will be
diagnosed, 1 million individuals will be hospitalized and 300,000 deaths will occur because
of HF. Approximately half of the deaths will be attributed to worsening pump function while
the remainder will be attributable to sudden cardiac death.
Biventricular (BIV) pacing has recently emerged as an exciting new treatment of advanced HF
with dramatic benefits to some patients. Current candidates include those with ventricular
conduction abnormalities and reduced ejection fraction who continue to suffer from severe HF
symptoms despite optimal pharmacological therapy. Recent clinical trials have demonstrated
that BIV pacing improves myocardial function, functional capacity, quality of life, as well
as reduces the incidence of hospitalization and even prolongs life. Despite all this, about
one third of patients with HF do not benefit from BIV pacing, the so-called 'non-responders'.
Our group and others have shown that there are direct genetic effects of BiV pacing in an
animal model, however, there are gaps in existing knowledge about the effects of left
ventricular (LV) pacing site or genetic influences on the degree of response to this novel
therapy.
This proposal aims at identifying predictors of benefit from Biventricular (BIV) pacing with
the goal of optimizing the degree of benefit and increasing the proportion of patients who
respond to this therapy. Patients who fulfill current indications for BIV pacing will undergo
and echocardiography (echo) with regional tissue Doppler analysis and cardiac imaging
consisting of a myocardial perfusion imaging(EGC rest gated Spect scan using Sestamibi) prior
to implantation of a BIV pacing device. They will then be randomly assigned to empiric versus
echo and Spect scan-guided LV lead positioning. In this latter group, optimal LV pacing site
will be defined as the site of latest peak tissue velocity by tissue Doppler echo and Spect
scan testing. In the empiric group, the LV lead position will be chosen by the masked
operator based on the coronary sinus venous anatomy, on electrocardiographic (ECG) criteria,
or other as per standard of care. Blood would be collected from all patients at the time of
the procedure for analysis of genetic polymorphisms.
individuals. It is estimated that in the next year nearly 400,000 new cases will be
diagnosed, 1 million individuals will be hospitalized and 300,000 deaths will occur because
of HF. Approximately half of the deaths will be attributed to worsening pump function while
the remainder will be attributable to sudden cardiac death.
Biventricular (BIV) pacing has recently emerged as an exciting new treatment of advanced HF
with dramatic benefits to some patients. Current candidates include those with ventricular
conduction abnormalities and reduced ejection fraction who continue to suffer from severe HF
symptoms despite optimal pharmacological therapy. Recent clinical trials have demonstrated
that BIV pacing improves myocardial function, functional capacity, quality of life, as well
as reduces the incidence of hospitalization and even prolongs life. Despite all this, about
one third of patients with HF do not benefit from BIV pacing, the so-called 'non-responders'.
Our group and others have shown that there are direct genetic effects of BiV pacing in an
animal model, however, there are gaps in existing knowledge about the effects of left
ventricular (LV) pacing site or genetic influences on the degree of response to this novel
therapy.
This proposal aims at identifying predictors of benefit from Biventricular (BIV) pacing with
the goal of optimizing the degree of benefit and increasing the proportion of patients who
respond to this therapy. Patients who fulfill current indications for BIV pacing will undergo
and echocardiography (echo) with regional tissue Doppler analysis and cardiac imaging
consisting of a myocardial perfusion imaging(EGC rest gated Spect scan using Sestamibi) prior
to implantation of a BIV pacing device. They will then be randomly assigned to empiric versus
echo and Spect scan-guided LV lead positioning. In this latter group, optimal LV pacing site
will be defined as the site of latest peak tissue velocity by tissue Doppler echo and Spect
scan testing. In the empiric group, the LV lead position will be chosen by the masked
operator based on the coronary sinus venous anatomy, on electrocardiographic (ECG) criteria,
or other as per standard of care. Blood would be collected from all patients at the time of
the procedure for analysis of genetic polymorphisms.
1. To test the hypothesis that the number, size, location, and severity of myocardial
perfusion defects and scar distribution dictate the pattern of LV dyssynchrony by tissue
Doppler echocardiography and speckle tracking. An extensive body of literature exists
describing the predictors of response to BIV pacing in HF patients. Our group and others
have established a clear association between the presence of mechanical cardiac
dyssynchrony and the response to BIV pacing. Also, our group and others have examined
the effect defects on myocardial perfusion imaging (MIBI) scan on response to BIV
pacing. What remains unclear is the relationship between the number, size, distribution,
and severity of these perfusion defects and the pattern of dyssynchrony by echo. It
seems plausible that the distribution of scar and/or perfusion abnormalities dictates
the pattern of mechanical delay and the relative timing of contraction of the various
parts of the LV. Approach: In this first phase of the proposal, we will utilize some of
the techniques that are available to our group to correlate the patterns of perfusion
defects with the patterns of mechanical dyssynchrony. For that purpose, patients with
clinical indications for BIV pacing will undergo nuclear perfusion imaging at rest as
well as echocardiographic (echo) imaging with tissue Doppler assessment and speckle
tracking. The site of latest mechanical activation and pattern of mechanical contraction
will then be compared to the sites of scar and/or perfusion defects on the resting MIBI
scan. Anticipated Results: The purpose of this first phase of the proposal would be to
identify if the dyssynchrony pattern is a downstream manifestation of the myocardial
injury scheme and therefore, if it can be predicted based on the number, size, severity,
and distribution of the perfusion abnormalities.
2. To test the hypothesis that LV lead positioning away from dense scars as determined by
resting nuclear perfusion imaging and close to the site of latest LV mechanical
activation translates into improved response after BIV pacing. Our group and others have
demonstrated improved acute hemodynamics and long term response to BIV pacing if the LV
lead position was concordant with the site of latest mechanical activation of the LV.
Also, our group and others have shown that an LV pacing lead positioned at the site of a
scar or in the vicinity of a high scar density area is associated with little
echocardiographic and clinical response after BIV pacing. To date, standard clinical
practice continues to consist of placing the LV lead tip in the most lateral and
posterior position. Maintaining this approach in all cardiomyopathy patients regardless
of the nature of the myocardial insult or the sites of scaring may not be optimal and
may account for the lack of response to BIV therapy in a significant number of patients.
The primary objective of this specific aim is to demonstrate that MIBI/echo-guided LV
lead placement is superior to standard lead placement and that patients who are
randomized to the MIBI/echo-guided arm will exhibit greater improvement in the symptoms
of HF and greater improvement of LV function at the 6-month interval compared to
patients receiving standard LV lead placement. Approach: Heart failure patients (n=210)
enrolled in this study will be randomly assigned in a 2:1 fashion to one of two study
arms:
perfusion defects and scar distribution dictate the pattern of LV dyssynchrony by tissue
Doppler echocardiography and speckle tracking. An extensive body of literature exists
describing the predictors of response to BIV pacing in HF patients. Our group and others
have established a clear association between the presence of mechanical cardiac
dyssynchrony and the response to BIV pacing. Also, our group and others have examined
the effect defects on myocardial perfusion imaging (MIBI) scan on response to BIV
pacing. What remains unclear is the relationship between the number, size, distribution,
and severity of these perfusion defects and the pattern of dyssynchrony by echo. It
seems plausible that the distribution of scar and/or perfusion abnormalities dictates
the pattern of mechanical delay and the relative timing of contraction of the various
parts of the LV. Approach: In this first phase of the proposal, we will utilize some of
the techniques that are available to our group to correlate the patterns of perfusion
defects with the patterns of mechanical dyssynchrony. For that purpose, patients with
clinical indications for BIV pacing will undergo nuclear perfusion imaging at rest as
well as echocardiographic (echo) imaging with tissue Doppler assessment and speckle
tracking. The site of latest mechanical activation and pattern of mechanical contraction
will then be compared to the sites of scar and/or perfusion defects on the resting MIBI
scan. Anticipated Results: The purpose of this first phase of the proposal would be to
identify if the dyssynchrony pattern is a downstream manifestation of the myocardial
injury scheme and therefore, if it can be predicted based on the number, size, severity,
and distribution of the perfusion abnormalities.
2. To test the hypothesis that LV lead positioning away from dense scars as determined by
resting nuclear perfusion imaging and close to the site of latest LV mechanical
activation translates into improved response after BIV pacing. Our group and others have
demonstrated improved acute hemodynamics and long term response to BIV pacing if the LV
lead position was concordant with the site of latest mechanical activation of the LV.
Also, our group and others have shown that an LV pacing lead positioned at the site of a
scar or in the vicinity of a high scar density area is associated with little
echocardiographic and clinical response after BIV pacing. To date, standard clinical
practice continues to consist of placing the LV lead tip in the most lateral and
posterior position. Maintaining this approach in all cardiomyopathy patients regardless
of the nature of the myocardial insult or the sites of scaring may not be optimal and
may account for the lack of response to BIV therapy in a significant number of patients.
The primary objective of this specific aim is to demonstrate that MIBI/echo-guided LV
lead placement is superior to standard lead placement and that patients who are
randomized to the MIBI/echo-guided arm will exhibit greater improvement in the symptoms
of HF and greater improvement of LV function at the 6-month interval compared to
patients receiving standard LV lead placement. Approach: Heart failure patients (n=210)
enrolled in this study will be randomly assigned in a 2:1 fashion to one of two study
arms:
Inclusion Criteria:
- age greater than 18 years Heart Failure Ejection fraction<35% QRS complex>120 ms
Exclusion Criteria:
- pregnant unable to consent
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